Understanding the genetic and neurobiological basis of aggression is important for human welfare, as pathological levels of aggression result in socially disruptive, violent behaviors. However, our understanding of the genetic mechanisms and the environmental triggers responsible for aggressive behavior is far from complete. The difficulty arises because aggression is a complex trait, affected by interacting ensembles of multiple genes whose expression depends on the environment, and because, until recently, it was difficult to quantify aggressive behavior in a model system amenable to high-throughput genetic analysis. We have developed a high-throughput, reproducible assay to quantify aggressive behavior in the genetic model organism, Drosophila melanogaster. The long-term goal of this research program is to identify networks of genes affecting Drosophila aggressive behavior, the subset of genes responsible for naturally occurring variation in aggression that are the substrate for evolutionary forces;and to determine how interactions between genetic networks and environmental factors shape the expression of aggressive behavior in Drosophila. In this project period, we will (1) screen a collection of 800 P-element insert lines that have been generated in a co-isogenic background to identify new genes affecting aggressive behavior, (2) conduct whole genome expression studies on P-element insert lines affecting aggressive behavior and artificial selection lines with increased and decreased levels of aggression, to identify co-regulated genetic networks affecting aggression, and test the model predictions;and (3) map quantitative trait loci affecting naturally occurring variation in aggressive behavior between lines selected for increased and decreased levels of aggressive behavior. Increased levels of aggression occur in alcoholics, Alzheimer's Disease patients, and individuals suffering from behavioral disorders, such as borderline personality disorder and intermittent explosive disorder. The social and economic costs to our society that result from violent behavior, and efforts to control it, are enormous. Determining what genetic factors affect aggressive behavior is challenging in humans, but can be addressed more readily in model organisms. Given the evolutionary conservation of function for fundamental traits, such as aggression, genes and pathways discovered in model organisms can be incorporated as candidate genes in human linkage and association studies.